Our sense of smell plays an important role in processing environmental cues. No two people perceive the olfactory world in exactly the same way, and differences in odor perception affect our food and product preferences, response to danger signals and poisons, and overall quality of life. This perceptual variation occurs, in part, because individuals have unique repertoires of olfactory receptors (ORs) that mediate odor perception. ORs are characterized by both genetic and functional variation, but we have little information regarding how this variation translates to differences in odor perception. The goal of this proposal is to examine how the removal of one OR alters perception of an odor. I will first identify genetic variation that alters odor perception in human subjects and relate these alterations to OR function via a heterologous assay. I will then reproduce OR loss-of-function by identifying small molecules that inhibit receptor function in vitro and examining their effect on odor perception in human subjects. Using these methods, I will establish a link between OR genotype, OR function, and human perception. The proposed experiments will provide crucial insight into two fundamental problems in the field: matching ORs to odorants and determining how ORs encode perceptual information. In addition, this work will help us understand the mechanisms underlying differences in odor perception and flavor preferences in human populations.